Non-immune therapy of IgA glomerulonephritis

Summary: The involvement of the IgA immune system and complement components in IgA glomerulonephritis (IgAGN) has prompted the use of immunosuppressive drugs in therapy, but none has so far been shown to alter the natural course of the disease. Because most patients with IgAGN present during the chronic phase of their illness, at the time when the initiating immune events may no longer be active, nonimmune therapy which targets the common pathway of progressive renal injury is likely to be more useful. There is increasing evidence that angiotensin-converting enzyme inhibitors (ACEI) reduce proteinuria and renal injury in patients with IgAGN, and this effect may be observed in both normotensive and hypertensive patients. Yet to be determined is whether this effect is specific for ACEI and whatever other effective antihypertensive drugs may achieve a similar result. Fish oil has recently been shown to retard the progression of renal failure in patients with aggressive IgAGN, but a narrow therapeutic window appears to exist for this form of treatment. Antiplatelet agents on their own appear to be ineffective but in combination with anticoagulation (low dose warfarin) have been shown to have an antiproteinuric effect and may preserve renal function in patients with progressive disease. Future directions of non-immune therapy of IgAGN include evaluation of the renoprotective effect of angiotensin II receptor antagonists, free-radical scavengers and antilipid drugs. More work should also be done to identify factors which put the patients at risk of developing progressive disease and which predict therapeutic response, as has been done recently with the identification of the deletion polymorphism of the angiotensin-converting enzyme gene as a marker of progressive disease and therapeutic response to ACEI in patients with IgAGN.     

Ultrastructural changes in the conjunctiva of Cynomolgus monkeys following pilocarpine administration?

After a slow-release pilocarpine carrier had been applied for three months, the conjunctival epithelium of two Cynomolgus monkeys showed some remarkable changes in the structure and distribution of the cell types as defined by the authors. The goblet cells (Type I) had almost entirely disappeared, whereas the epithelial cells with secretion granules (Type II) had considerably increased in number. The morphology of the Type II cells gave clear indications of a very active metabolism. In a control experiment, in which two Cynomolgus monkeys treated with a 4% pilocarpine solution for three months, these ultrastructural changes did not occur; it must therefore be assumed that mechanical irritation of the conjunctiva was the cause.     

Bullous dermatosis with conjunctival and corneal involvement: differential diagnostic scope and explanation of the "overlap syndrome" concept

Chronic blister-forming dermatosis can lead to conjunctival and corneal involvement. Taking one such case as an example, the authors show that while disorders of this kind can be classified as a form of bullous dermatosis, the differential diagnostic classification is not unequivocal, regardless of the examination method adopted. The term "overlay syndrome" has been introduced into the dermatologic literature to cover clinical pictures of this kind.     

Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB

Usher syndrome is recognized as the most frequent cause of hereditary deaf-blindness. Usher syndrome type I (USH1), the most severe form of the disease, is characterized by profound congenital sensorineural deafness, constant vestibular dysfunction, and retinitis pigmentosa of prepubertal onset. This form is genetically heterogeneous and five loci (USH1A-E) have been mapped thusfar. However, only the gene responsible for USH1 B (which accounts for approximately 75% of USH1 cases) has been characterized. It encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted 2215 amino acid sequence. Primers covering the complete myosin VIIA coding sequence as well as the 3' non coding sequence were designed, allowing direct sequence analysis of each of the 48 coding exons and flanking splice sites in seven patients affected by USH1. Four novel mutations were thereby identified. The possibility should now be considered of a sequence-based prenatal diagnosis in some of the families affected by this very severe form of Usher syndrome.